Abstract：
Although male factor accounts for 40%-50% of unintended childlessness, we are far from fully understanding the detailed causes. Usually, affected men cannot even be provided with a molecular diagnosis.
We aimed at a higher resolution of the human sperm proteome for better understanding of the molecular causes of male infertility. We were particularly interested in why reduced sperm count decreases fertility despite many normal-looking spermatozoa and which proteins might be involved.
Applying mass spectrometry analysis, we qualitatively and quantitatively examined the proteomic profiles of spermatozoa from 76 men differing in fertility. Infertile men had abnormal semen parameters and were involuntarily childless. Fertile subjects exhibited normozoospermia and had fathered children without medical assistance.
We discovered proteins from about 7000 coding genes in the human sperm proteome. These were mainly known for involvements in cellular motility, response to stimuli, adhesion, and reproduction. Numbers of sperm proteins showing at least threefold deviating abundances increased from oligozoospermia (N = 153) and oligoasthenozoospermia (N = 154) to oligoasthenoteratozoospermia (N = 368). Deregulated sperm proteins primarily engaged in flagellar assembly and sperm motility, fertilization, and male gametogenesis. Most of these participated in a larger network of male infertility genes and proteins.
We expose 31 sperm proteins displaying deviant abundances under infertility, which already were known before to have fertility relevance, including ACTL9, CCIN, CFAP47, CFAP65, CFAP251 (WDR66), DNAH1, and SPEM1. We propose 18 additional sperm proteins with at least eightfold differential abundance for further testing of their diagnostic potential, such as C2orf16, CYLC1, SPATA31E1, SPATA31D1, SPATA48, EFHB (CFAP21), and FAM161A.
Our results shed light on the molecular background of the dysfunctionality of the fewer spermatozoa produced in oligozoospermia and syndromes including it. The male infertility network presented may prove useful in further elucidating the molecular mechanism of male infertility.
We aimed at a higher resolution of the human sperm proteome for better understanding of the molecular causes of male infertility. We were particularly interested in why reduced sperm count decreases fertility despite many normal-looking spermatozoa and which proteins might be involved.
Applying mass spectrometry analysis, we qualitatively and quantitatively examined the proteomic profiles of spermatozoa from 76 men differing in fertility. Infertile men had abnormal semen parameters and were involuntarily childless. Fertile subjects exhibited normozoospermia and had fathered children without medical assistance.
We discovered proteins from about 7000 coding genes in the human sperm proteome. These were mainly known for involvements in cellular motility, response to stimuli, adhesion, and reproduction. Numbers of sperm proteins showing at least threefold deviating abundances increased from oligozoospermia (N = 153) and oligoasthenozoospermia (N = 154) to oligoasthenoteratozoospermia (N = 368). Deregulated sperm proteins primarily engaged in flagellar assembly and sperm motility, fertilization, and male gametogenesis. Most of these participated in a larger network of male infertility genes and proteins.
We expose 31 sperm proteins displaying deviant abundances under infertility, which already were known before to have fertility relevance, including ACTL9, CCIN, CFAP47, CFAP65, CFAP251 (WDR66), DNAH1, and SPEM1. We propose 18 additional sperm proteins with at least eightfold differential abundance for further testing of their diagnostic potential, such as C2orf16, CYLC1, SPATA31E1, SPATA31D1, SPATA48, EFHB (CFAP21), and FAM161A.
Our results shed light on the molecular background of the dysfunctionality of the fewer spermatozoa produced in oligozoospermia and syndromes including it. The male infertility network presented may prove useful in further elucidating the molecular mechanism of male infertility.
摘要：
背景：尽管男性因素占意外无子女的40-50％，我们还远远没有完全了解详细的原因。通常,受影响的男性甚至不能提供分子诊断。
目的：这项研究的目的是获得更高分辨率的人类精子蛋白质组，以更好地了解男性不育的分子原因。我们特别感兴趣的是，尽管许多看起来正常的精子，为什么精子数量减少会降低生育能力，以及可能涉及哪些蛋白质。
方法：应用质谱分析，我们定性和定量检测了76名不同生育能力的男性精子的蛋白质组学特征.不育男性的精液参数异常，并且不由自主地无子女。有生育能力的受试者表现出正常精子症，并且在没有医疗帮助的情况下生了孩子。
结果：我们在人类精子蛋白质组中发现了大约7,000个编码基因的蛋白质。这些主要以参与细胞运动而闻名，对刺激的反应,附着力,和繁殖。从少精子症（n=153）和少弱精子症（n=154）到少弱精子症（n=368），显示至少三倍偏离丰度的精子蛋白数量增加。主要参与鞭毛组装和精子运动的精子蛋白失调，受精,和雄性配子发生。其中大多数参与了男性不育基因和蛋白质的更大网络。
结论：我们暴露了31种在不育症下表现出异常丰度的精子蛋白，之前已经知道有生育相关性，包括ACTL9，CCIN，CFAP47,CFAP65,CFAP251(WDR66),DNAH1和SPEM1。我们提出了18种额外的精子蛋白，其丰度差异至少为8倍，用于进一步测试其诊断潜力。例如C2orf16、CYLC1、SPATA31E1、SPATA31D1、SPATA48、EFHB(CFAP21)，FAM161A
结论：我们的研究结果揭示了在少精子症及其综合征中产生的精子功能失调的分子背景。提出的男性不育网络可能有助于进一步阐明男性不育的分子机制。本文受版权保护。保留所有权利。
目的：这项研究的目的是获得更高分辨率的人类精子蛋白质组，以更好地了解男性不育的分子原因。我们特别感兴趣的是，尽管许多看起来正常的精子，为什么精子数量减少会降低生育能力，以及可能涉及哪些蛋白质。
方法：应用质谱分析，我们定性和定量检测了76名不同生育能力的男性精子的蛋白质组学特征.不育男性的精液参数异常，并且不由自主地无子女。有生育能力的受试者表现出正常精子症，并且在没有医疗帮助的情况下生了孩子。
结果：我们在人类精子蛋白质组中发现了大约7,000个编码基因的蛋白质。这些主要以参与细胞运动而闻名，对刺激的反应,附着力,和繁殖。从少精子症（n=153）和少弱精子症（n=154）到少弱精子症（n=368），显示至少三倍偏离丰度的精子蛋白数量增加。主要参与鞭毛组装和精子运动的精子蛋白失调，受精,和雄性配子发生。其中大多数参与了男性不育基因和蛋白质的更大网络。
结论：我们暴露了31种在不育症下表现出异常丰度的精子蛋白，之前已经知道有生育相关性，包括ACTL9，CCIN，CFAP47,CFAP65,CFAP251(WDR66),DNAH1和SPEM1。我们提出了18种额外的精子蛋白，其丰度差异至少为8倍，用于进一步测试其诊断潜力。例如C2orf16、CYLC1、SPATA31E1、SPATA31D1、SPATA48、EFHB(CFAP21)，FAM161A
结论：我们的研究结果揭示了在少精子症及其综合征中产生的精子功能失调的分子背景。提出的男性不育网络可能有助于进一步阐明男性不育的分子机制。本文受版权保护。保留所有权利。
